[Federal Register Volume 81, Number 183 (Wednesday, September 21, 2016)]
[Notices]
[Pages 64914-64916]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-22660]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2011-P-0081]


Armenpharm, Ltd.; Suspension of Approval of an Abbreviated New 
Drug Application for Chloramphenicol Capsules, 250 Milligrams; 
Determination That CHLOROMYCETIN (Chloramphenicol) Capsules, 50 
Milligrams and 100 Milligrams, and Three Other Products Were Withdrawn 
From Sale for Reasons of Safety or Effectiveness

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is suspending 
approval of abbreviated new drug application (ANDA) 060851 for 
chloramphenicol capsules, 250 milligrams (mg), held by Armenpharm, Ltd. 
(Armenpharm), 49 South Ridge Rd., P.O. Box D1400, Pomona, NY 10970. FDA 
has also determined that CHLOROMYCETIN (chloramphenicol) Capsules, 50 
mg and 100 mg; AMPHICOL (chloramphenicol) Capsules, 100 mg; and 
CHLOROMYCETIN PALMITATE (chloramphenicol palmitate) Oral Suspension, 
150 mg/5 milliliters (mL), were withdrawn from sale for reasons of 
safety or effectiveness. The Agency will not accept or approve ANDAs 
for

[[Page 64915]]

chloramphenicol capsules, 50 mg and 100 mg, or chloramphenicol 
palmitate oral suspension, 150 mg/5 mL.

DATES: Effective September 21, 2016.

FOR FURTHER INFORMATION CONTACT: Nicole Mueller, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6312, Silver Spring, MD 20993-0002, 301-
796-3601.

SUPPLEMENTARY INFORMATION:

I. Background

    In 1984, Congress enacted the Drug Price Competition and Patent 
Term Restoration Act of 1984 (Pub. L. 98-417) (the 1984 amendments), 
which authorized the approval of duplicate versions of drug products 
approved under an ANDA procedure. ANDA applicants must, with certain 
exceptions, show, among other requirements, that the drug for which 
they are seeking approval contains the same active ingredient in the 
same strength and dosage form as the ``listed drug,'' which is a 
version of the drug that was previously approved. ANDA applicants do 
not have to repeat the extensive clinical testing otherwise necessary 
to gain approval of a new drug application (NDA).
    The 1984 amendments include what is now section 505(j)(7) of the 
Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355(j)(7)), 
which requires FDA to publish a list of all approved drugs. FDA 
publishes this list as part of the ``Approved Drug Products With 
Therapeutic Equivalence Evaluations,'' which is generally known as the 
``Orange Book.'' Under FDA regulations, a drug is removed from the list 
if the Agency withdraws or suspends approval of the drug's NDA or ANDA 
for reasons of safety or effectiveness or if FDA determines that the 
listed drug was withdrawn from sale for reasons of safety or 
effectiveness (21 CFR 314.162).
    Under Sec.  314.161(a) (21 CFR 314.161(a)), the Agency must 
determine whether a listed drug was withdrawn from sale for reasons of 
safety or effectiveness: (1) Before an ANDA that refers to that listed 
drug may be approved, (2) whenever a listed drug is voluntarily 
withdrawn from sale and ANDAs that refer to the listed drug have been 
approved, and (3) when a person petitions for such a determination 
under 21 CFR 10.25(a) and 10.30. FDA may not approve an ANDA that does 
not refer to a listed drug.
    Section 505(j)(6) of the FD&C Act authorizes FDA to suspend 
approval of an ANDA if the listed drug relied upon has been withdrawn 
from sale for what FDA determines are safety or effectiveness reasons. 
Section 314.161(d) provides that if FDA determines that a listed drug 
was withdrawn from sale for safety or effectiveness reasons, the Agency 
will initiate proceedings under Sec.  314.153(b) (21 CFR 314.153(b)) 
that could result in the suspension of approval of the ANDAs that refer 
to the listed drug.

II. Chloramphenicol Capsules, 250 mg

    On February 7, 2011, Armenpharm submitted a citizen petition under 
Sec.  10.30 (Docket No. FDA-2011-P-0081), requesting that the Agency 
determine whether CHLOROMYCETIN (chloramphenicol) Capsules, 250 mg 
(ANDA 060591), was withdrawn from sale for reasons of safety or 
effectiveness. CHLOROMYCETIN (chloramphenicol) Capsules, 250 mg, is the 
listed drug that was the basis of submission for Armenpharm's ANDA 
060851 for chloramphenicol capsules, 250 mg. In the Federal Register of 
July 13, 2012 (77 FR 41412), FDA published a notice stating its 
determination under Sec.  314.161 that CHLOROMYCETIN (chloramphenicol) 
Capsules, 250 mg, was withdrawn from sale for reasons of safety or 
effectiveness. FDA also notified Armenpharm of the Agency's decision in 
a letter dated July 13, 2012.
    Pursuant to Sec.  314.153(b)(1), FDA initiated the process to 
suspend Armenpharm's chloramphenicol ANDA 060851 by sending a letter, 
dated December 3, 2015, notifying Armenpharm of the Agency's initial 
determination that CHLOROMYCETIN (chloramphenicol) Capsules, 250 mg, 
was withdrawn for reasons of safety or effectiveness and its initial 
decision to suspend approval of ANDA 060851 (see Docket No. FDA-2011-P-
0081). Under Sec.  314.153(b)(2), Armenpharm had 30 days from that 
notification in which to present written comments or information 
bearing on the initial decision. On December 17, 2015, Armenpharm 
submitted comments requesting an oral hearing under Sec.  
314.153(b)(4). However, on March 17, 2016, Armenpharm withdrew its oral 
hearing request.
    Therefore, under section 505(j)(6) of the FD&C Act and Sec.  
314.153(b), and under authority delegated by the Commissioner to the 
Director, Center for Drug Evaluation and Research, approval of ANDA 
060851, and all amendments and supplements thereto, is suspended (see 
DATES). FDA has removed all chloramphenicol capsules, 250 mg, from the 
list of drug products published in the Orange Book, and no 
chloramphenicol capsules, 250 mg, will be listed in the Orange Book. 
Distribution of chloramphenicol capsules, 250 mg, in interstate 
commerce without an approved application is illegal and subject to 
regulatory action (see sections 505(a) and 301(d) of the FD&C Act (21 
U.S.C. 355(a) and 331(d)).

III. Other Discontinued Oral Chloramphenicol Drug Products

    FDA has become aware that the oral chloramphenicol drug products 
listed in the table in this document are no longer being marketed.

------------------------------------------------------------------------
        Application No.                 Drug              Applicant
------------------------------------------------------------------------
ANDA 060591....................  CHLOROMYCETIN       Parkedale
                                  (chloramphenicol)   Pharmaceuticals
                                  Capsules, 50 mg     Inc. (formerly
                                  and 100 mg.         Parke Davis
                                                      Pharmaceutical
                                                      Research Division
                                                      of Warner Lambert
                                                      Co.).
ANDA 062301....................  CHLOROMYCETIN       Parkedale
                                  PALMITATE           Pharmaceuticals
                                  (chloramphenicol    Inc. (formerly
                                  palmitate) Oral     Parke Davis
                                  Suspension,         Pharmaceutical
                                  Equivalent to       Research Division
                                  (EQ) 150 mg base/   of Warner Lambert
                                  5 mL.               Co.).
ANDA 060058....................  AMPHICOL            John J. Ferrante.
                                  (chloramphenicol)
                                  Capsules, 100 mg.
NDA 050152.....................  CHLOROMYCETIN       Parkedale
                                  PALMITATE           Pharmaceuticals
                                  (chloramphenicol    Inc. (formerly
                                  palmitate) Oral     Parke Davis
                                  Suspension, EQ      Pharmaceutical
                                  150 mg base/5mL.    Research Division
                                                      of Warner Lambert
                                                      Co.).
------------------------------------------------------------------------

    FDA has reviewed its records and, under Sec.  314.161, has 
determined that the drug products listed in this table were withdrawn 
from sale for reasons of safety or effectiveness. We have carefully 
reviewed Agency records concerning the withdrawal from sale of the drug 
products listed in the table. We have also independently evaluated 
relevant literature and data for possible postmarketing adverse events. 
At the time of the approval of the drug

[[Page 64916]]

products listed in the table, there was significant unmet medical need. 
With the approval of additional therapies with less severe adverse drug 
effects, FDA has determined that the risks associated with 
CHLOROMYCETIN (chloramphenicol) Capsules, 50 mg and 100 mg; AMPHICOL 
(chloramphenicol) Capsules, 100 mg; and CHLOROMYCETIN PALMITATE 
(chloramphenicol palmitate) Oral Suspension, 150 mg/5 mL, as currently 
labeled, outweigh the benefits. Most important, CHLOROMYCETIN 
(chloramphenicol) Capsules, 50 mg and 100 mg; AMPHICOL 
(chloramphenicol) Capsules, 100 mg; and CHLOROMYCETIN PALMITATE 
(chloramphenicol palmitate) Oral Suspension, 150 mg/5 mL, may cause a 
number of adverse reactions, the most serious being bone marrow 
depression (anemia, thrombocytopenia, and granulocytopenia temporally 
associated with treatment). A boxed warning in the prescribing 
information for chloramphenicol sodium succinate injection and 
chloramphenicol capsules and oral suspension states that serious 
hypoplastic anemia, thrombocytopenia, and granulocytopenia are known to 
occur after administration of chloramphenicol. The drug product 
labeling recommends extensive safety monitoring, including baseline 
blood studies followed by periodic blood studies approximately every 2 
days during therapy. The boxed warning also describes fatal aplastic 
anemia associated with administration of the drug and aplastic anemia 
attributed to chloramphenicol that later terminated in leukemia. 
Published literature suggests that the risk of fatal aplastic anemia 
associated with oral formulations of chloramphenicol may be higher than 
the risk associated with the intravenous formulation.
    FDA has also reviewed approved labeling for the products and has 
determined that a Risk Evaluation and Mitigation Strategy (REMS) would 
be required to ensure that the benefits of the drug outweigh its risks. 
The REMS may include Elements to Assure Safe Use, including restricted 
distribution, and a Medication Guide could be required as part of the 
labeling. FDA has determined that additional nonclinical and possibly 
clinical studies of safety and efficacy would be necessary before 
CHLOROMYCETIN (chloramphenicol) Capsules, 50 mg and 100 mg; AMPHICOL 
(chloramphenicol) Capsules, 100 mg; and CHLOROMYCETIN PALMITATE 
(chloramphenicol palmitate) Oral Suspension, 150 mg/5 mL, could be 
considered for reintroduction to the market.
    Accordingly, the Agency will remove CHLOROMYCETIN (chloramphenicol) 
Capsules, 50 mg and 100 mg; AMPHICOL (chloramphenicol) Capsules, 100 
mg; and CHLOROMYCETIN PALMITATE (chloramphenicol palmitate) Oral 
Suspension, 150 mg/5 mL, from the list of drug products published in 
the Orange Book. FDA will not accept or approve ANDAs that refer to 
these drug products.

    Dated: September 14, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-22660 Filed 9-20-16; 8:45 am]
 BILLING CODE 4164-01-P